REGIOSELECTIVE OXIDATION OF STEROIDS
329
Oxidation of 4 and 5 (control reactions). The benzoates 4 and 5 were oxidized
using condition identical to the ones indicated for the oxidation of substrate 2. Final
reaction conditions: substrate 1 mM, catalyst 0.5 mM, Cu2+ 2 mM, PhIO 10 eq. The
reaction was quenched and worked up in the usual way. The products were quantified
in the crude by 1H NMR and HPLC and then isolated by preparative TLC (silica gel,
CH2Cl2:MeOH, 95:5) and identified by MS and NMR as indicated below.
Identification of the Products
1
15-Hydroxy-3-oxo-5␣-androstan-17-yl 2,2Ј-bipyridine-5-carboxylate (6). H
NMR (500 MHz, CDCl3) (selected peaks): ␦ ϭ 9.29 (br s, 1H), 8.72 (d, J ϭ 4 Hz,
1H), 8.49 (m, 2H), 8.40 (dd, J1 ϭ 8 Hz, J2 ϭ 2 Hz, 1H), 7.86 (dt, J1 ϭ 8 Hz,
J2 ϭ 2 Hz, 1H), 7.37 (m, 1H), 4.83 (t, J ϭ 8 Hz, 1H, 17␣-H), 4.34 (m, 1H,
15␣-H), 1.25 (s, 3H, 18-Me), 1.09 (s, 3H, 19-Me). ESI-MS: 489 (M ϩ 1). COSY:
Protons at 4.83 and 4.84 ␦ are both coupled to a common peak at 2.86 ␦ (16-H),
confirming that the new CH–OH is on C15. The calculated chemical shift values for
the methyls are
15␣-OH derivative: 18-Me ϭ 1.01␦, 19-Me ϭ 1.05␦
15-OH derivative: 18-Me ϭ 1.25␦, 19-Me ϭ 1.07␦, so it can be concluded that
the product is the 15-OH derivative.
1
16␣-Hydroxy-3-oxo-5␣-androstan-17-yl 2,2Ј-bipyridyl-5-carboxylate (7). H
NMR (500 MHz, CDCl3) (selected peaks): ␦ ϭ 9.29 (br s, 1H), 8.72 (d, J ϭ 4 Hz,
1H), 8.49 (m, 2H), 8.40 (dd, J1 ϭ 8 Hz, J2 ϭ 2 Hz, 1H), 7.86 (dt, J1 ϭ 8 Hz,
J2 ϭ 2 Hz, 1H), 7.37 (m, 1H), 4.50 (d, J ϭ 4.5 Hz, 1H, 17␣-H), 4.30 (m, 1H,
16-H), 1.05 (s, 3H, 19-Me), 1.03 (s, 3H, 18-Me). ESI-MS: 489 (M ϩ 1). COSY:
Protons at 4.50 and 4.30 ␦ are coupled to each other, confirming that the new CH–OH
is on C16. The calculated Me shift values are
16␣-OH derivative: 18-Me ϭ 0.99␦, 19-Me ϭ 1.03␦
16-OH derivative: 18-Me ϭ 1.23␦, 19-Me ϭ 1.06␦, so it can be concluded that
the product is the 16␣-OH derivative.
1
3,15-Dioxo-5␣-androstan-17-yl 2,2Ј-bipyridyl-5-carboxylate (8). H NMR (500
MHz, CDCl3) (selected peaks): ␦ ϭ 9.29 (br s, 1H), 8.72 (d, J ϭ 4 Hz, 1H), 8.49
(m, 2H), 8.40 (dd, J1 ϭ 8 Hz, J2 ϭ 2 Hz, 1H), 7.86 (dt, J1 ϭ 8 Hz, J2 ϭ 2 Hz,
1H), 7.37 (m, 1H), 5.24 (t, J ϭ 10 Hz, 1H, 17␣-H), 2.95 (m, 1H, C16-H), 2.28 (m,
1H, C16-H), 1.05 (s, 3H, 19-Me), 1.06 (s, 3H, 18-Me). ESI-MS: 487 (M ϩ 1). COSY:
The two protons at 2.95 and 2.28 ␦ that are next to the new carbonyl are coupled to
each other as well as to 17␣-H, indicating the 15-oxo substitution. Calculated chemical
shifts: 18-Me ϭ 1.06␦, 19-Me ϭ 1.05␦.
1
6␣-Hydroxy-3-oxo-5␣-androstan-17-yl benzoate (9). H NMR (500 MHz, CDCl3)
(selected peaks): ␦ ϭ 8.03 (d, J ϭ 7.5 Hz, 2H), 7.54 (t, J ϭ 7.5 Hz, 1H), 7.43
(t, J ϭ 7.5 Hz, 2H), 4.85 (t, J ϭ 8 Hz, 1H, 17␣-H), 3.50 (m, 1H, 6-H), 1.05 (s,
3H, 19-Me), 0.96 (s, 3H, 18-Me). ESI-MS: 411 (M ϩ 1). Calculated chemical shifts:
18-Me ϭ 0.96␦, 19-Me ϭ 1.07␦.
1
5␣-Hydroxy-3-oxo-androstan-17-yl benzoate (10). H NMR (500 MHz, CDCl3)
(selected peaks): ␦ ϭ 8.04 (d, J ϭ 7.5 Hz, 2H), 7.56 (t, J ϭ 7.5 Hz, 1H), 7.44
(t, J ϭ 7.5 Hz, 2H), 4.85 (t, J ϭ 8 Hz, 1H, 17␣-H), 2.70 (d, J ϭ 15 Hz, 1H, 4-H),
2.12 (d, J ϭ 15 Hz, 1H, 4␣-H), 1.20 (s, 3H, 19-Me), 0.96 (s, 3H, 18-Me). COSY: